Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

1.3K
Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
1.3K
Insulin Secretory Vesicles01:05

Insulin Secretory Vesicles

5.0K
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
5.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

3.6K
The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.6K
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

1.3K
The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
1.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Structure of the melatonin-related orphan receptor, GPR50.

Molecules and cells·2026
Same author

Multimodal antigenic escape to GPRC5D-targeted T cell engagers in multiple myeloma.

Nature medicine·2026
Same author

CaliciBoost: Performance-driven evaluation of molecular representations for caco-2 permeability prediction.

Journal of cheminformatics·2025
Same author

EGFR activation requires cholesterol interaction at the inner leaflet of the plasma membrane.

Science advances·2025
Same author

Structural mechanism of insulin receptor activation by a dimeric aptamer agonist.

Experimental & molecular medicine·2025
Same author

Super-photostable organic dye for long-term live-cell single-protein imaging.

Nature methods·2025

Related Experiment Video

Updated: Jul 15, 2025

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
07:30

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion

Published on: May 10, 2018

9.3K

A stepwise activation model for the insulin receptor.

Na-Oh Yunn1, Junhong Kim2, Sung Ho Ryu2

  • 1Postech Biotech Center, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. beback13@postech.ac.kr.

Experimental & Molecular Medicine
|October 1, 2023
PubMed
Summary
This summary is machine-generated.

Insulin receptor (IR) activation is complex. This review explores IR structures with ligands and aptamers, proposing a sequential activation model and discussing biased agonists for targeted therapies.

More Related Videos

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
05:58

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

Published on: June 25, 2019

7.5K
Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
08:32

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Published on: January 4, 2018

10.4K

Related Experiment Videos

Last Updated: Jul 15, 2025

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
07:30

Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion

Published on: May 10, 2018

9.3K
Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate
05:58

Measuring Relative Insulin Secretion using a Co-Secreted Luciferase Surrogate

Published on: June 25, 2019

7.5K
Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain
08:32

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Published on: January 4, 2018

10.4K

Area of Science:

  • Biochemistry
  • Structural Biology
  • Pharmacology

Background:

  • Insulin receptor (IR) activation initiates crucial metabolic and mitogenic signaling pathways.
  • While inactive and fully active IR structures are known, early activation steps remain unclear.
  • Understanding IR activation is key for metabolic disease research.

Purpose of the Study:

  • To elucidate the early activation mechanisms of the insulin receptor.
  • To review structural and functional data of IR in complex with various ligands.
  • To propose a model for sequential IR activation and discuss biased agonists.

Main Methods:

  • Structural analysis of partially activated IR-aptamer complexes.
  • Functional analysis of IR in complex with diverse ligands.
  • Review of existing structural and functional data.

Main Results:

  • Structures of partially activated IR offer insights into initial conformational changes.
  • A sequential activation model for the insulin receptor is proposed.
  • Biased agonists selectively activating metabolic pathways are discussed.

Conclusions:

  • The early activation mechanism of the insulin receptor is better understood through structural studies.
  • A sequential model explains IR activation by various ligands.
  • Selective agonists hold potential for targeted therapeutic strategies in metabolic diseases.